The survival of patients harboring malignant gliomas has increased over the past 15 years from a median of about 6 months with surgery and some radiation therapy (RT), to over a year with vigorous multimodality therapy consisting of extensive resection, high-dose RT and long-term chemotherapy. This improvement has been statistically confirmed by controlled prospective trials of the Brain Tumor Study Group, which has also identified prognostically important clinical variables in the patients. It is proposed to continue these studies under the Brain Tumor Cooperative Group (BTCG) as follows: I. To increase good-quality survival by performing Phase III and Phase II clinical trials. The first Phase III trial will randomize newly diagnosed and operated patients into a four-arm (2 x 2 factorial) study consisting of (a) RT plus intravenous (iv) BCNU, (b) RT plus iv BCNU plus iv 5-Fluorouracil (5-FU), (c) RT plus intracarotid (ic) BCNU, or (d) RT plus ic BCNU plus iv 5-FU. The first phase II trial will (1) randomize previously resected and radiated nonprogressive patients, and progressive patients without prior chemotherapy, to (a) ic Cisplatin or (b) iv Interferon; and (2) randomize progressive patients with prior chemotherapy (after re-operation as needed) to (a) stereotactic interstitial RT with 125I seeds, or (b) oral Procarbazine. II. To study prognostic variables, CT scans and pathological changes in the patients over the course of their disease. III. To study long-term consequences of therapy including RT/chemotherapy induced neurological and non-neurological effects. IV. To perform an in vitro/in vivo correlation study determining chemosensitivity on tumor specimens from the initial surgical resection and correlating this with the survival of the patient after treatment on BTCG protocols. This study will include Phase III patients from throughout the group, the in vitro studies to be performed at Memorial Sloan/Kettering Cancer Center.